Rejection of K1735 murine melanoma in syngeneic hosts requires expression of MHC class I antigens and either class II antigens or IL-2

Tumor specific immunity is mediated by CTL that recognize peptide Ag in the context of MHC class I molecules and by Th cells that recognize peptide Ag in the context of MHC class II molecules. To clarify the relative importance of MHC class I and II Ag in tumor rejection, we transfected a K1735 melanoma that did not express constitutively either MHC class I or II Ag with H-2K^k and/or I-A^k genes and determined their tumorigenicity. K1735 transfectants expressing either K^k or A^k Ag alone produced tumors in normal C3H mice, whereas most transfectants that expressed both molecules were rejected in normal C3H mice but produced tumors in nude mice. However, the A^k Ag requirement can be substituted by IL-2 because transfection of K^k-positive/A^k-negative K1735 cells with the IL-2 gene also resulted in abrogation of tumorigenicity in normal C3H mice but not in nude mice. Similarly, transfection of K^k-negative/A^k-positive K1735 cells with IFN-γgene resulted in induction of MHC class I Ag as well as rejection of these tumors in normal C3H mice. The rejection of K1735 transfectants expressing K^k and A^k Ag in normal C3H mice required both CD4⁺ and CD8⁺ T cells. In addition, the transplantation immunity induced by K1735 transfectants expressing both K^k and A^k Ag completely cross-protected mice against challenge with K^k-positive transfectants but only weakly protected them against challenge with parental K1735 cells or A^k-positive transfectants. These results indicate that expression of either MHC class I or II Ag alone is insufficient to cause the rejection of K1735 melanoma in syngeneic hosts and that both Ag are necessary. In addition, our data suggest that the failure of K^k-positive K1735 cells to induce a primary tumor rejection response in normal C3H mice may result from their inability to induce the helper arm of the antitumor immune response.